Undifferentiated Small Cells Research Articles

Central Nervous System Primitive Neuroectodermal Tumor of Spinal Cord Developing 20 Years After Curative Treatment of Pineal Tumor -Case Report-

A 65-year-old male who had previously received curative treatment for a pineal tumor presented with an extremely rare case of primary central nervous system (CNS) primitive neuroectodermal tumor (PNET) of the spinal cord manifesting as progressive tetraparesis. Although the histology was not verified, highly radiosensitive tumor was suspected because of the benign clinical course for over 20 years after only radiation therapy. Magnetic resonance imaging demonstrated an intramedullary tumor extending from C5 to T1. He underwent partial resection and histological examination revealed blue tumor with undifferentiated small round cells. Immunohistochemically, c-kit was negative but CD99 was strongly and diffusely positive. Therefore, rearrangement of the Ewing sarcoma gene was examined to determine the presence of peripheral type of PNET. The results were negative and systemic workup revealed no other disease. These findings led to the diagnosis of primary intramedullary CNS PNET of the spinal cord, and suggested that the spinal cord tumor occurred independently of the prior pineal disease. The residual tumor was controlled by postoperative local radiation therapy.

Atypical teratoid/rhabdoid tumor of the central nervous system: clinicopathologic and immunohistochemical features of four cases

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare aggressive infantile neoplasm of uncertain origin. This study was performed to assess the clinicopathologic and immunohistochemical features of four AT/RT cases. Two cases were male and two were female, and their ages ranged from 8 to 103 months. Tumors were located in the cerebellum (two cases), frontoparietal lobe (one case), and third ventricle (one case). Histopathologically, the tumors were composed of rhabdoid cells and undifferentiated small cells mixed with epithelial or mesenchymal components. However, one of the tumors was composed predominantly of a mesenchymal component mimicking a sarcoma. Immunohistochemically, vimentin (4/4), epithelial membrane antigen (4/4), cytokeratin (3/4), smooth muscle actin (4/4), glial fibrillary acidic protein (4/4), S-100 (4/4), and synaptophysin (1/4) were positive in varying proportions, while desmin and INI-1 were negative in all the cases. All of the patients died within a mean of 14 months due to tumor progression despite the chemotherapy. Only one of our patients lived for 40 months after the diagnosis. In conclusion, AT/RTs are aggressive tumors. They can occur in a variety of locations, such as the third ventricle. Morphologically, a large spectrum can be seen, like predominantly sarcoma in appearance, but immunohistochemistry is helpful in the correct diagnosis.

Tumor desmoplásico de células pequeñas redondas. Morfología atípica en la glándula submaxilar

Desmoplastic small round cell tumour (DSRCT) is a rare disease usually affecting young males. There are no other articles with a sub-maxillary location. The tumour consists of nests and masses of undifferentiated small round cells embedded in a desmoplastic stroma. The co-expression of epithelial, muscular and neuronal antigens distinguishes this entity from other small round cell tumours. The t(11;22)(p13;q12) translocation is a recurrent characteristic of this type of tumour.We report a case of desmoplastic small round cell tumour of the sub-maxillary gland, with an evolution of 8months, affecting a 36year old male. He suffered chronic lymphatic leukaemia five years ago and needed a bone marrow transplant. There was a 4×3cm tumour. There were no signs of malignancy on the CT scan. A right sub-maxillectomy was performed. The pathology analysis gave a diagnosis of DSRCT. Post-surgical radiotherapy was given.The definitive diagnosis was reached using immunohistochemical techniques, such as polyphenotypical differentiation (epithelial, mesenchymal and neural), and by demonstration of translocation (11;22)(p13;q12). Sub-maxillary location is very rare.

Perigastric extraskeletal Ewing’s sarcoma: A case report

Ewing's sarcoma (ES) is a neoplasm of undifferentiated small round cells, which occurs in the bones and deep soft tissues of children and adolescents. We present a rare case of a 44-year-old woman with gastric ES presenting with epigastric pain and weight loss. Ultrasound and computed tomography scans indicated a solid/cystic mass in the pancreatic tail. At laparotomy, the tumor was found attached to the posterior surface of the stomach, completely free from the pancreas, with no lymphadenopathy or local metastases. The polynodal, partly pseudocystic, dark-red soft tumor was excised. Histopathology revealed an anaplastic small-round-cell tumor with strong membranous CD99 immunoexpression. Additionally, there was patchy immunostaining for S-100 protein, vimentin, protein gene product (PGP) 9.5 and neuron-specific enolase, and weak focal CD117 cytoplasmic immunoreactivity. The patient had no adjuvant chemotherapy; her postoperative recovery was uneventful, and she remains symptom-free, and without any sign of recurrence at 20 mo. To the best of our knowledge, this is only the third ever case of gastric ES.

Small round cell desmoplastic tumour. Atypical morphology in the sub-maxillary gland

Desmoplastic small round cell tumour (DSRCT) is a rare disease usually affecting young males. There are no other articles with a sub-maxillary location. The tumour consists of nests and masses of undifferentiated small round cells embedded in a desmoplastic stroma. The coexpression of epithelial, muscular and neuronal antigens distinguishes this entity from other small round cell tumours. The t(11;22) (p13;q12) translocation is a recurrent characteristic of this type of tumour.We report a case of desmoplastic small round cell tumour of the sub-maxillary gland, with an evolution of 8 months, affecting a 36-year-old male. He suffered chronic lymphatic leukaemia 5 years ago and needed a bone marrow transplant. There was a 4×3cm tumour. There were no signs of malignancy on the CT scan. A right submaxillectomy was performed. The pathology analysis gave a diagnosis of DSRCT. Post-surgical radiotherapy was given.The definitive diagnosis was reached using immunohistochemical techniques, such as polyphenotypical differentiation (epithelial, mesenchymal, and neural), and by demonstration of translocation (11;22) (p13;q12). Sub-maxillary location is very rare.

Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes

Embryonal tumors with abundant neuropil and true rosettes (ETANTR) comprise a rare variant of embryonal brain tumors usually occurring in infants. Only 13 cases have been reported in the literature to date and little is known about the molecular pathogenesis of these tumors. Here, we describe a case of ETANTR in a 2-year-old girl presenting with a large tumor in the vermis of the cerebellum. Histological examination showed clusters of small-undifferentiated cells including ependymoblastic-like rosettes admixed with large fibrillar and paucicellular neuropil-like areas indicative for ETANTR. Genomic imbalances were detected by using array-based comparative genomic hybridization. In addition to trisomy of chromosome 2, which has been previously described in ETANTR, array-CGH revealed high-level genomic amplification of 0.89 Mb at chromosome band 19q13.42 covering a microRNA cluster and several protein-coding genes. This aberration has not been described in any other brain tumor to date, indicating a specific aberration in ETANTR. MicroRNAs contained in the microRNA cluster at 19q13.42 including oncomirs miRNA-372 and miRNA-373 were highly up-regulated in the tumor when compared to normal cerebellum or whole brain. In summary, this is the first report on a potentially specific genetic aberration in ETANTR, supporting the hypothesis of a distinct tumor entity.

Congenital Ewing sarcoma in retroperitoneum with multiple metastases

A 7-day-old Japanese female showed the absence of spontaneous movement in her both legs. MRI revealed tumors in the retroperitoneum invading into the spinal canal, the left cerebral hemisphere and the right eyeball. Histological examination of retroperitoneal tumor revealed the sheets of undifferentiated small round cells with hyperchromatic nuclei and scanty cytoplasm. EWS-FLI1 fusion gene was detected by RT-PCR, indicating Ewing sarcoma. She received chemo-radiotherapy and survived for 2 years and 10 months despite the multiple metastases at initial presentation.

Congenital Intracranial Mesenchymal Chondrosarcoma: Case Report and Review of the Literature in Pediatric Patients

In this paper we report the 1st case of a congenital intracranial mesenchymal chondrosarcoma in a 2-month-old infant, apparently present at birth. A magnetic resonance image showed a large left parietal solid mass, while microscopy revealed a mixture of undifferentiated small cells and mature hyaline cartilage islands, positive for vimentin, S-100, and CD99. A surgical excision was performed but the patient died after a few weeks as a result of a rapid relapse of the tumor. We also review the pediatric cases (in patients less than 20 years old) of extraskeletal (intracranial) mesenchymal chondrosarcomas of the literature, with a focus on the most recent cytogenetic and immunohistochemical studies.

A case of congenital supratentorial tumor: Atypical teratoid/rhabdoid tumor or primitive neuroectodermal tumor?

Two embryonal CNS tumors, atypical teratoid/rabdoid tumor (AT/RT) and primitive neuroectodermal tumor (PNET), may be confused with each other and misdiagnosed. Here we report an infant with a congenital supratentorial tumor, which was detected by fetal MRI at 37 weeks gestation. On routine histological examination, the tumor was composed mainly of small undifferentiated cells, among which many rhabdoid cells and occasional sickle-shaped embracing cells were observed. No mesenchymal or epithelial areas were evident. Our impression was that the tumor was an atypical example of AT/RT. Immunohistochemically, almost all the tumor cells were strongly positive for vimentin. However, epithelial membrane antigen was notably negative, and most of the tumor cell nuclei were clearly positive for INI1. In addition, many tumor cells were positive for neurofilament protein. There were also occasional small areas containing many tumor cells positive for glial fibrillary acidic protein. Finally, a diagnosis of PNET, with a rhabdoid phenotype and expression of neuronal and glial markers, was made. In the present case, application of INI1 immunostaining was very helpful for distinguishing PNET from AT/RT.

A true “triphasic” pattern: thoracolumbar spinal tumor in a young dog

An 8-month-old male Bernese Mountain Dog was referred with a history of hindlimb weakness that progressed to paresis on the right side. An intradural mass was detected in the spinal canal at the level of the 2nd and 3rd lumbar vertebrae. During surgical removal, 2 small fragments of the mass were prepared for cytologic examination by the squash technique. Cytologic examination revealed 3 different cell types: mesenchymal (stromal) cells, epithelial cells, and small undifferentiated hyperchromatic cells. On the basis of location and the triphasic cytologic pattern, a diagnosis of spinal nephroblastoma (thoracolumbar spinal tumor of young dogs) was made; histologic examination of the mass confirmed the cytologic diagnosis. To our knowledge, this is the first report of a triphasic pattern in a cytologic sample; recognizing this pattern is an important aid in reaching a definitive cytologic diagnosis.

Malignant Teratoid/Rhabdoid Tumour: Long-Term Survival

The patient is a previously healthy 19-month-old child who became symptomatic in October 1998 with right hand weakness and cessation of new words with progression of right sided weakness and decreased sensation over the next month. The computed tomography (CT) and magnetic resonance imaging (MRI) scans demonstrated a large, deep, left frontal periventricular enhancing mass with several cystic areas. A left frontoparietal craniotomy was performed and the tumour was grossly resected. The pathological diagnosis was AT/RT. Grossly, the tumour was composed of firm, pink-tan hemorrhagic tissue. Sections showed a densely cellular, infiltrating neoplasm with areas of necrosis (some calcified), fascicular and focal sheets of collagen, and a variable, often prominent reticulin network. There was no endothelial proliferation. Light microscopy with hematoxylin and eosin stain (Figure 1) revealed a varied tumour appearance predominantly composed of larger tumour cells, with randomly dispersed nests of small undifferentiated cells close to the interface of tumour and normal brain tissue. The larger cells had several growth patterns: some were loosely arranged bi- or multi-polar cells forming cords and acinar structures against a faintly basophilic mucinous background, some were elongated cells arranged in coarse follicles or other compact bundles, while others were arranged in sheets or nests with prominent, sometimes glassy eosinophilic and cytoplasmic inclusions and eccentric nuclei (rhabdoid cells). Larger cells had nuclei with vesicular chromatin and prominent nucleoli, and smaller cells had hyperchromatic nuclei. Mitoses were focally numerous with some atypical in form, and cytoplasmic glycogen was inconspicuous. Immunohistochemical studies revealed widespread staining for epithelial membrane antigen (EMA), vimentin (Figure 2), glial fibrillary acid protein (GFAP), groups of cells with membranous patterns of staining for CD99, regional staining for neuron-specific enolase (NSE), scattered staining for transthyretin, and rare staining for actin, cytokeratin, and synaptophysin. The tumour was positive for chromosome 22 monosomy. Electron microscopy showed polygonal cells arranged in ill-defined acini that formed inconspicuous, sometimes entwined short microvillus processes. Variable numbers of intermediate filaments were identified and some cells showed a rudimentary basal lamina. Desmosomes were not seen, and there was no evidence of neural differentiation.

Desmoplastic Small Round Cell Tumor of the Kidney in Childhood

Desmoplastic small round cell tumor (DSRCT) is a rare malignant tumor that generally manifests as abdominal paraserosal masses and affects mainly male adolescents and young adults. When presenting within visceral organs, the diagnosis of DSRCT poses significant difficulties. Four primary renal DSRCT in children diagnosed during a 3-year period are the basis of this report. The medical records and pathologic material were reviewed, including immunohistochemical, ultrastructural, and cytogenetic/molecular studies. The age at presentation was 6 to 8 years, and all children presented with a left renal mass. The tumors measured 3.7 to 13.4 cm and consisted of nests, cords, or sheets of small undifferentiated cells with foci of necrosis and calcification. Desmoplasia was not seen. Tumor cells were immunopositive for vimentin, WT-1 (monoclonal and polyclonal), desmin, cytokeratin, and epithelial membrane antigen. A distinct paranuclear dotlike pattern was observed with vimentin and desmin. Tumor cells possessed rare or focal immunoreactivity for platelet derived growth factor-A and transforming growth factor-beta3, which have been implicated in the pathogenesis of desmoplasia in DSRCT. The EWS-WT1 t(11;22)(p13;q12) translocation was demonstrated in all 4 tumors by fluorescence in situ hybridization and/or reverse transcription-polymerase chain reaction. DSRCT should be considered in the differential diagnosis of renal tumors composed of small round cells. Undifferentiated morphology and lack of desmoplasia contribute to the difficulty in its recognition. Ancillary studies such as immunohistochemistry may suggest the diagnosis, but cytogenetic and molecular genetic studies are required for confirmation.

Tumor intraabdominal desmoplásico de células pequeñas y redondas: Revisión de la literatura a propósito de un caso con estudio citológico, histopatológico, inmunohistoquímico y molecular

Purpose: To review the cyto-histopathological, immunohistochemical and molecular characteristics of small round cell desmoplastic tumor (DSRCT). Material and methods: A 18 year old male with an intraabdominal epigastric mass. Results: The tumor consisted of nests and masses of undifferentiated small round cells embedded in a desmoplastic stroma, with areas of rosette formation immuno-reactive to cytokeratins, vimentin, desmin, enolase, and WT1 fraction of the EWS/WT1 fusion protein transcript. The molecular study demonstrated the existence of the translocation t(11 ;22)(p 13 ;q 12). Conclusions: The solid areas and rosette formation have been described in other cases of DSRCT. The chimeric transcription product can be detected by RT-PCR, Southern-blot, Western-blot, and immunohistochemistry. Cytology is especially useful in recurrences. The differential diagnosis should be made with the small round undifferented cell tumors group.

Immunohistochemical detection of myogenin and p21 in methylcholanthrene‐induced mouse rhabdomyosarcomas

3-Methylcholanthrene (MC)-induced 10 embryonal (ERSs) and 24 pleomorphic rhabdomyosarcomas (PRSs) of the dermis in mouse were examined immunohistochemically for myogenin, p21 and proliferating cell nuclear antigen (PCNA) nuclear reactivity and myosin reactivity. ERSs had higher expression of myogenin and p21 compared with that of myosin. PRSs were divided into two groups having high (moderate or marked reactivity; HLM) and low (mild reactivity; LLM) levels of myosin expression. Expression of p21 was higher in HLM-PRSs than in LLM-PRSs. Statistically significant association was observed between myosin and p21 expression in PRSs, but not between myosin and myogenin expression. Myogenin and p21 reactivity were observed in myoblast-like cells, but rarely in multinucleated cells. In ERSs, small undifferentiated myogenic precursor cells were also positive for p21. No difference of PCNA reactivity was observed between HLM-PRSs and LLM-PRSs, although its reactivity was higher in PRSs than in ERSs. The results suggest that myogenin is related to myoblast-like cell differentiation in PRSs and that p21 plays essential roles in myotube formation and myosin expression. In ERSs, p21 may be involved in inhibition of myogenic precursor cell proliferation and differentiation.

Diffuse high-grade gliomas as second malignant neoplasms after radio-chemotherapy for pediatric malignancies

Diffuse high-grade gliomas are known to develop in children after cranial irradiation for other malignancies. Here, clinicopathological characteristics are outlined. Nine children received cranial irradiation and chemotherapy for medulloblastoma (n=2) or acute lymphoblastic leukemia (n=7). They developed a high-grade glioma 7-14 years thereafter. Clinical charts, radiologic findings, and pathologic specimens were reviewed. Archival material was stained immunohistochemically. Gliomas evolving as second malignant neoplasms show peculiarities and differ in some aspects from their "spontaneous" counterparts. Most are supratentorial, contrast-enhancing, space-occupying lesions. They are composed mainly of small undifferentiated cells, which are mainly negative for glial fibrillary acidic protein and positive for microtubule associated proteins 2 (MAP2). Epidermal growth factor receptor labeling could not be detected in any of them. Ki67-labeling was usually high, whereas p53- and h-ras p21-staining was variable. The median survival was only 12 months despite intensive treatment.

Um novo modelo de isolamento do tumor de Walker utilizando o gradiente de Ficoll-Hypaque

The purpose was to evaluate a novel technique for isolation of Walker's tumoral cells using a Ficoll-Hypaque gradient and its further influence on tumor development. Twenty male Wistar rats have been divided in 2 groups: G1= without ficoll, G2= with ficoll. Tumor was excised, homogenized and suspended in lactate ringer. A sample of the cell suspension was adjusted at a concentration of 1x10(6) cells/ml (G1). A second sample was centrifuged on a Ficoll-Hypaque gradient and the cell concentration was then adjusted (G2). Tumor was implanted by subcutaneous injection of 1.0 ml in the right armpit of rats. Tumor volume (TV) and tumor weight (TW) were compared in two groups. There were no differences between the two groups in TV (G1=17.9+/-3.8 cm3 vs. G2=17.2+/-4.4 cm3; p=0.190) and TW (G1=7.0+/-1.8 g vs. G2=7.3+/-2.8 g; p=0.569). The histological analysis showed similar patterns of infiltration by small-undifferentiated cells and necrosis in both groups. However, a mild to moderate granulocytic exudate was more frequent in the animals whose tumors derived from Ficoll-isolated cells. Hemorrhage from slight to moderate was only observed in this group. A Ficoll-Hypaque gradient can provide more adequate isolation of Walker's tumor and the cell suspension obtained by this technique has lower contamination by other cell types.

Morphology and histology of P. argentinus (Crustacea, Decapoda, Caridea) digestive tract

This work describes the morphology and histology of the P. argentinus digestive tract. The foregut comprises the mouth, oesophagus, and stomach and is lined by a simple cylindrical epithelium overlain by cuticle. There are tegumental glands in the oral region and in the first portion of the oesophagus and of the hindgut. The cardiac stomach is an oval dorsal sac in the cephalothorax and has no calcified structures. The pyloric stomach comprises an upper chamber and a lower gland filter. The filter consists of an outer row of elongated setae and an inner row of dorsally curved setae forming longitudinal channels 16-18 microm wide. The midgut runs from the dorsal chamber of the pyloric stomach to the sixth abdominal somite without caeca. The hindgut runs from the sixth abdominal somite to the ventral anus. The mid-gut epithelium comprises dominant cylindrical cells and small undifferentiated cells in the first portion. The hindgut wall presents longitudinal folds, conspicuous muscular bundles, and a folded cuticle. The digestive tract of P. argentinus is basically similar to that of most of decapods. The absence of calcified structures in the stomach and the width of the longitudinal channels in the filter are related to the predominantly detritivorous diet.

Lung Metastasis from an Immature Teratoma of the Nasal Cavity Masquerading as Small Cell Carcinoma of the Lung

We report a case of small cell lung cancer that turned out to be a metastatic teratoma from the nasal cavity rather than a new primary cancer. A 54-year-old woman was diagnosed with an immature teratoma of the nasal cavity with a predominant neuroblastomatous component. Small cell lung cancer was detected by bronchoscopic biopsy 21 months later, and it was treated with concurrent radiochemotherapy as if it had been a new primary cancer. Since a recurrent tumor containing fat-like density grew slowly on the serial chest CT scans after achieving complete response, we reached the conclusion that the small undifferentiated cells could be metastatic neuroblastomatous components from the immature teratoma of the nasal cavity.

Pediatric embryonal tumor of the cerebellum with rhabdoid cells and novel intracytoplasmic inclusions: distinction from atypical teratoid/rhabdoid tumor

We report a case of embryonal tumor with novel inclusion bodies occurring in the cerebellum of a 12-year-old girl. The tumor was histopathologically composed of small undifferentiated cells intermingled with a small number of rhabdoid cells, which had an ultrastructural feature of intermediate filament whorls. Immunohistochemically, the neoplasm showed a polyphenotype, including glial fibrillary acidic protein (GFAP), S-100, synaptophysin, chromogranin A, cytokeratin, vimentin, smooth muscle actin, and desmin. However, epithelial membrane antigen (EMA) immunoreactivity was absent. The MIB-1 labeling index was high (25.6%). Ultrastructurally, there was no evidence of neuronal or myogenic differentiation. The small neoplastic cells contained numerous small intracytoplasmic inclusions stained pink by eosin and red by Masson's trichrome stain. The inclusion body was a densely packed, granulovesicular structure at the electron microscopic level, and was immunoreactive for vimentin, GFAP, desmin, and actin. Reverse transcription-PCR and immunohistochemistry showed the expression of INI1 at the RNA and protein levels, respectively. In conclusion, this tumor was differentiated from atypical teratoid/rhabdoid tumor by the absence of EMA and the presence of INI1 mRNA and protein, and diagnosed as an unclassified, embryonal tumor. Eosinophilic, granulovesicular inclusions of the tumor cells are novel cytoplasmic inclusions in the brain tumor.

Pancreatic rhabdomyosarcoma

A 21-year-old Japanese woman was hospitalized because of epigastric pain of 3 months' duration. CT demonstrated a slightly hypodense, 2.5-cm-diameter mass in the head of the pancreas (A). Routine laboratory tests, carcinoembyonic antigen, carbohydrate associated antigen 19-9, insulin, glucagon, gastrin, and somatostatin levels were within normal ranges. ERCP demonstrated compression of the main and the accessory pancreatic ducts (B) and a normal cholangiogram. Endosonographically, the mass was well defined and had an irregular margin; the internal echo texture was generally hypoechoic except for a heterogeneous hypoechoic area in the center (C). EUS-guided FNA was performed, and microscopic assessment of the aspirate revealed nests of undifferentiated small, round or spindle-shaped cells in proliferative connective tissue (D; H&E, orig. mag. ×200). Immunohistochemical staining was positive for cytoplasmic myoglobin (E; orig. mag. ×200) and desmin; there was no reactivity to S100, NSE, chromagranin, or synaptophysin. A diagnosis of rhabdomyosarcoma of the head of the pancreas was made.